Masitinib May Slow Disability Progression in Progressive MS

December 2022

The progressive forms of multiple sclerosis (MS) may be mechanistically different from relapsing forms of the disease. New therapies are needed because only 1 drug has been approved for primary progressive MS and none for the nonactive form of secondary progressive MS.

Masitinib is an oral tyrosine kinase inhibitor that inhibits the activity of microglia, macrophages, and mast cells in the central nervous system. Investigators recently reported the results of an international, phase 3, double-blind, randomized clinical trial for the efficacy and safety of masitinib in slowing disease progression in patients with progressive MS who had progressing but not clinically active disease.

The study was comprised of 2 parallel studies lasting 96 weeks: in study 1, patients were randomly assigned to receive 4.5 mg/kg daily of oral masitinib or placebo. In study 2, a dose-titration study, patients were randomized to receive 4.5 mg/kg daily of oral masitinib for 12 weeks followed by titration to 6.0 mg/kg daily or placebo. The primary outcome was disability progression on the Expanded Disability Status Scale compared with baseline.

A total of 611 adults aged 18 to 75 years with primary progressive MS or nonactive secondary progressive MS who had disability progression without relapse during the previous 2 years were included in the studies. Between 40% and 45% of these patients had primary progressive MS, and approximately half of all patients used walking aids.

For the primary end point, the investigators found that treatment with 4.5 mg/kg daily of masitinib was associated with slower disability progression and a significantly better disability score change from baseline compared with the placebo group (P = .026). The treatment benefit was similar for both progressive forms of MS.

For secondary end points, the change in scores for upper limb motor skills for patients in study 1 was significantly lower compared with the placebo group (P = .039); however, no significant differences were seen between groups on walking, cognitive, or quality-of-life tests.

In contrast to study 1 (single-dose study), no significant differences in disability progression for the masitinib study 2 (titration study) were seen compared with the placebo titration group. The investigators believe this was caused by an unexpected improvement in disability scores over the first 36 weeks in the primary progressive MS subgroup that received the placebo.

Adverse events with masitinib were similar to those seen in previous studies. Serious treatment-emergent adverse events occurred in approximately twice as many patients in the masitinib groups versus the placebo groups. The most common serious treatment-emergent adverse events associated with masitinib were maculopapular rash in the single-dose study and maculopapular rash and neutropenia in the dose-titration study. Discontinuations due to adverse events were also higher in the single-dose masitinib group compared with the placebo group.

The investigators concluded that overall, “benefit was demonstrated in a relatively diverse population that comprised both primary progressive MS and nonactive secondary progressive MS subgroups.” They suggested that additional phase 3 studies for masitinib for the treatment of progressive MS are warranted to replicate their results.


Vermersch P, Brieva-Ruiz L, Fox RJ, et al. Efficacy and safety of masitinib in progressive forms of multiple sclerosis: a randomized, phase 3, clinical trial. Neurol Neuroimmunol Neuroinflamm. 2022;9(3):e1148.

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